title: Sp1 mediates microRNA-29c-regulated type I collagen production in renal tubular epithelial cells.
abstract: Specificity protein 1 (Sp1), a ubiquitously expressed transcription factor, plays a potential pathogenic role for fibrotic disease in many organs by regulating the expression of several fibrosis-related genes, however, its role in kidney fibrosis and the mechanisms regulating its expression remain incompletely clarified. Here, we found that Sp1 was markedly induced and closely correlated with interstitial type I collagen accumulation in kidney tubular epithelia from obstructive nephropathy. In vitro, both Sp1 and type I collagen expression were up-regulated in TGF-β1-treated kidney tubular epithelial cells (NRK-52E), whereas knockdown of Sp1 largely abolished TGF-β1-induced type I collagen production, suggesting that Sp1 induction is partially responsible for type I collagen expression. In addition, we found that miR-29c expression was remarkably reduced in either the tubular epithelial cells from kidney with UUO nephropathy or TGF-β1-treated NRK-52E cells. Knockdown of miR-29c could sufficiently induce Sp1 and type I collagen expression, whereas ectopic expression of miR-29c largely abolished their expression stimulated by TGF-β1 in NRK-52E cells. Furthermore, knockdown of Sp1 effectively hindered type I collagen induction stimulated by miR-29c down-regulation. Collectively, this study demonstrates that Sp1 acts as an essential mediator for miR-29c in regulating type I collagen production in tubular epithelial cells, which may provide a novel mechanistic insight about miR-29c in renal fibrosis.
authors.affiliation: Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210003, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Mingxia
authors.initials: M
authors.lastname: Xiong
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Ping
authors.initials: P
authors.lastname: Wen
authors.forename: Hongdi
authors.initials: H
authors.lastname: Cao
authors.forename: Junwei
authors.initials: J
authors.lastname: Yang
authors.forename: Chunsun
authors.initials: C
authors.lastname: Dai
authors.forename: Weichun
authors.initials: W
authors.lastname: He
mesh_terms: D000818:Animals; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor
keywords: ECM; MicroRNA-29c; Renal fibrosis; Sp1; Specificity protein 1; TGF; Tubular epithelial cell; Type I collagen; UTR; UUO; excessive extracellular matrix; miR; microRNA; siRNA; small interfering RNA; specificity protein 1; transforming growth factor; unilateral ureteral obstruction; untranslated region